Effect of protein on the absorption of phenytoin through everted gut preparations

Area of Science:

• Pharmacokinetics
• Gastrointestinal Physiology
• Drug Absorption

Background:

• Phenytoin bioavailability can be influenced by various factors, including gastrointestinal conditions.
• Understanding drug transfer across the gut membrane is crucial for predicting oral absorption.
• The role of luminal contents, such as proteins, in modulating drug dissolution and absorption is not fully elucidated.

Purpose of the Study:

• To investigate the effect of protein on phenytoin transfer across an everted gut membrane model.
• To determine how pH influences the interaction between protein, phenytoin solubility, and drug transfer.
• To explore the implications of these findings for phenytoin bioavailability in the presence of food.

Main Methods:

• Everted gut membrane model was used to measure phenytoin transfer.
• Phenytoin transfer was assessed from both solutions and dissolving media at varying pH.
• The effect of introducing protein into the mucosal medium on phenytoin transfer was evaluated.

Main Results:

• Protein binding in the mucosal solution generally decreased the apparent transfer rate of phenytoin.
• At pH 4, protein presence increased both phenytoin solubility and dissolution rate.
• This increase in solubility and dissolution at pH 4 led to enhanced phenytoin transfer rates.

Conclusions:

• Protein binding significantly impacts phenytoin transfer across the gut membrane.
• The effect of protein is pH-dependent, influencing solubility and dissolution.
• These pH-dependent effects of protein may contribute to the observed influence of food on phenytoin bioavailability.